Respiratory mucous glycoprotein (MGP) is secreted in a variety of acute and chronic disease states: secretion is strongly influenced by inflammatory mediators, but the mechanisms by which MGP is influenced are unclear. The capacity of activated human neutrophils (PMN) to stimulate respiratory mucous glycoprotein secretion from human airways in vitro was studied. Purified PMN activated with opsonized zymosan stimulate the release of MGP from human airways in a dose-dependent manner. One neutral protease, neutrophil elastase in nanogram/ml concentrations, stimulates the release of MGP and this effect is blocked by specific elastase antagonists. Elastase antagonists do not block the effect of supernatants from activated PMN on MGP secretion. Current work is directed at identifying the products released during neutrophil activation which stimulate MGP secretion. Information available to date suggests that the molecule responsible is large (70,000-100,000 molecular weight) and work is progressing on HPLC purification of the molecule. The significance of this work lies in the identification of inflammatory mediators which might stimulate MGP secretion in vivo in such states as acute and chronic bronchitis, asthma, and cystic fibrosis.